Hyaluronic acid (hereinafter referred to as HA) or its sodium salt is a kind of natural polymer mucopolysaccharide substance, which is widely distributed in mammalian connective tissue, comb and the capsules of Streptococcus. Since having no specificity of species and organs, the HA gel prepared from HA has good body compatibility when transplanted or injected to the body as a filler, having the functions of anti-wrinkling, breast enlargement and padding but without any side effects on human body. Therefore, it is widely used in medicine and beauty. The skill fillers made from HA or its sodium salts are most popular in the plastic surgery. These tissue fillers, similar to collagen, have a longer efficacy and lower risk of allergic reactions. However, HA or its sodium salt is easy to degrade in vivo due to the function of HA hydrolase and free radicals, thus, its in vivo retention time is short. To enhance in vivo retention time of HA or its sodium salt, usually HA or its sodium salt is crosslinked, so that the hydroxyl group in the polymer chain of HA or its sodium salt is chemically bonded with the cross-linking agent to prepare the cross-linked HA or its sodium salt gel. In order not to affect the biocompatibility of the gel, the concentration of cross-linking agent should not be too high. But when the consumption of cross-linking agent is low, the resulting gel derivative has a low resistance to the in vivo hydrolysis, the in vivo retention time is short, usually about 1-6 months. When the consumption of cross-linking agent is excessive, the in vivo retention time is extended, but the viscosity is high and the gel hardness is increased, not easy to pass the needles of 30G even 27G with a decreased injectability. In addition, when the consumption of cross-linking agent is high, excessive cross-linking agent will remain in the product, difficult to clean and purify, which makes the cytotoxicity of the cross-linked HA or its sodium salt gel greater and easy to produce side effect on human body. The cross-linking reaction of the existing HA or its sodium salt is performed in a homogeneous aqueous alkaline solution, which can enhance the anti-biodegradability by improving the degree of cross-linking and extend the in vivo retention time of skin filler. Thus, it will, on the one hand, undermine the biocompatibility of cross-linked HA or its sodium salt gel, and on the other hand, reduce the viscoelasticity of gel products, increase the hardness and decrease the injectability.